ArticleNature2018
SAMHD1 acts at stalled replication forks to prevent interferon induction.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 289 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
289 citing papers in PubMed, 2 syntheses or guidelines pooled it, 442 citations in OpenAlex.
- Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.Nature genetics · 2023Pooled it
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- TREX1 limits anti-tumor immunity by degrading short cytosolic DNA molecules.EMBO reports · 2026Article
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- Exploiting DNA damage tolerance for precision oncology.Trends in cancer · 2026Review
- The Significance of cGAS-STING Signaling in Response to Oncogenic Viruses.Cell biochemistry and function · 2026Review
- p21 (CDKN1A) Is the Major Driver of Sulforaphane-Mediated Reduction in SAMHD1 T592 Phosphorylation in Macrophages.Biomolecules · 2026Article
- Molecular mechanisms regulating cGAS/STING activation in health and disease.The Journal of clinical investigation · 2026Review
- DPY30 Is an Epigenetic Decoupler Linking Replication Stress to Immunoediting in Pancreatic Cancer.Cancer research · 2026Article
- A toxic STING-SAMHD1 axis drives replication stress in progeria and cancer cells.Nucleic acids research · 2026Article
- Targeting RNase H2: A dual-mechanism strategy to elevate replication stress, DNA damage, and antitumor immunity in TNBC.Cell reports. Medicine · 2026Article
- Condensin and topoisomerases cooperate to relieve topological stress at stalled replication forks.Nature communications · 2026Article
- ATM counteracts chromatin-bound cGAS during DNA replication.Nature cell biology · 2026Article
- cGAS-STING pathway in lung cancer and emerging therapeutic approaches.Drug discovery today · 2026Review
- Interferon stimulatory DNA activates the DNA damage signaling through ATM and DNA-PK sensing.The Journal of biological chemistry · 2026Article
- Article
- STING causes replication stress and nascent DNA degradation via SAMHD1.bioRxiv : the preprint server for biology · 2026Article
- Glycosylation as a dynamic regulator of RLR and cGAS-STING innate immune signalling pathways.Communications biology · 2026Review
- Telomere Crisis Shapes Cancer Evolution.Cold Spring Harbor perspectives in biology · 2026Review
- SAMHD1 depletion restricts SARS-CoV-2 infection by suppressing HNF1-dependent ACE2 expression in lung epithelial cells.PLoS pathogens · 2026Article
229 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SAMHD1 was previously characterized as a dNTPase that protects cells from viral infections. Mutations in SAMHD1 are implicated in cancer development and in a severe congenital inflammatory disease known as Aicardi-Goutières syndrome. The mechanism by which SAMHD1 protects against cancer and chronic inflammation is unknown. Here we show that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11. This function activates the ATR-CHK1 checkpoint and allows the forks to restart replication. In SAMHD1-depleted cells, single-stranded DNA fragments are released from stalled forks and accumulate in the cytosol, where they activate the cGAS-STING pathway to induce expression of pro-inflammatory type I interferons. SAMHD1 is thus an important player in the replication stress response, which prevents chronic inflammation by limiting the release of single-stranded DNA from stalled replication forks.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.